Selective photosensitization of human leukemic cells by a pyrene-containing fatty acid.
Irradiation with long-wave UV light (LUV) at 366 nm of cells that had been incubated with 12-(1-pyrene)dodecanoic acid (P12), a fatty acid derivative with a covalently linked pyrene nucleus, resulted in cytotoxicity. Using the in vitro established human cell lines HL-60 and U-937, we demonstrated that these leukemic cells are much more susceptible to the photosensitizing effect of P12 than normal bone marrow (BM); a 4-log reduction in the number of clonogenic leukemic cells was achieved under conditions where colony formation by normal hemopoietic progenitors was reduced by less than 40%. Moreover, the results of irradiating mixed populations of leukemic and normal cells indicated that phototoxicity of leukemic cells was not affected by the presence of a large excess of normal BM cells, nor was the survival of normal BM cells influenced by the presence of leukemic cells. These findings suggested that the procedure could be adapted for selective ex vivo elimination of malignant cells, i.e., purging of BM in remission prior to autologous transplantation.
Fibach
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Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Gatt
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Rachmilewitz
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D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007850:Lauric Acids / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D010787:Photosensitivity Disorders / Q000139:chemically induced* / Q000473:pathology
D007850:Lauric Acids; C040596:12-(1-pyrene)dodecanoic acid